Differential role of natural killer group 2D in recognition and cytotoxicity of hepatocyte-like cells derived from embryonic stem cells and induced pluripotent stem cells.

Stem cell-based approaches have the potential to address the organ shortage in transplantation. Whereas both embryonic stem cells and induced pluripotent stem cells have been utilized as cellular sources for differentiation and lineage specification, their relative ability to be recognized by immune effector cells is unclear. We determined the expression of immune recognition molecules on hepatocyte-like cells (HLC) generated from murine embryonic stem cells and induced pluripotent stem cells, compared to adult hepatocytes, and we evaluated the impact on recognition by natural killer (NK) cells. We report that HLC lack MHC class I expression, and that embryonic stem cell-derived HLC have higher expression of the NK cell activating ligands Rae1, H60, and Mult1 than induced pluripotent stem cell-derived HLC and adult hepatocytes. Moreover, the lack of MHC class I renders embryonic stem cell-derived HLC, and induced pluripotent stem cell-derived HLC, susceptible to killing by syngeneic and allogeneic NK cells. Both embryonic stem cell-derived HLC, and induced pluripotent stem cell-derived HLC, are killed by NK cells at higher levels than adult hepatocytes. Finally, we demonstrate that the NK cell activation receptor, NKG2D, plays a key role in NK cell cytotoxicity of embryonic stem cell-derived HLC, but not induced pluripotent stem cell-derived HLC.

Cdc42 GTPase and Rac1 GTPase act downstream of p120 catenin and require GTP exchange during gastrulation of zebrafish mesoderm.

BACKGROUND: We investigated the roles of p120 catenin, Cdc42, Rac1, and RhoA GTPases in regulating migration of presomitic mesoderm cells in zebrafish embryos. p120 catenin has dual roles: It binds the intracellular and juxtamembrane region of cadherins to stabilize cadherin-mediated adhesion with the aid of RhoA GTPase, and it activates Cdc42 GTPase and Rac1 GTPase in the cytosol to initiate cell motility. RESULTS: During gastrulation of zebrafish embryos, knockdown of the synthesis of zygotic p120 catenin δ1 mRNAs with a splice-site morpholino caused lateral widening and anterior-posterior shortening of the presomitic mesoderm and somites and a shortened anterior-posterior axis. These phenotypes indicate a cell-migration effect. Co-injection of low amounts of wild-type Cdc42 or wild-type Rac1 or dominant-negative RhoA mRNAs, but not constitutively-active Cdc42 mRNA, rescued these p120 catenin δ1-depleted embryos. CONCLUSIONS: These downstream small GTPases require appropriate spatiotemporal stimulation or cycling of GTP to guide mesodermal cell migration. A delicate balance of Rho GTPases and p120 catenin underlies normal development.

Veterinarians' perceptions of COVID-19 pandemic-related influences on veterinary telehealth and on pet owners' attitudes toward cats and dogs.

OBJECTIVE: To gather and evaluate veterinarians' perspectives about the impacts of the COVID-19 pandemic on the use of veterinary telehealth and on cat owners' versus dog owners' attitudes toward transmission of the SARS-CoV-2 virus from their pets. SAMPLE: 93 respondent veterinarians (47 in primary care practice and 46 in specialty practice). PROCEDURES: An online survey was conducted between June 15 and July 15, 2020, and included 21 questions concerning demographics, use of telehealth before and after the onset of the pandemic (before March 15, 2020, and between March 15 and June 15, 2020, respectively), changes in caseloads, and perception of clients' concerns about potential for transmission of the SARS-CoV-2 virus from pets. Reported zip codes informed the collection of census data. RESULTS: The level of poverty was significantly lower in zip code areas for respondents who reported telehealth services were (vs were not) offered before the pandemic. The percentage of respondents who reported their practice offered telehealth services increased from 12% (11/93) before the pandemic to 38% (35/93) between March 15 and June 15, 2020. Although most respondents reported owner-expressed concerns over SARS-CoV-2 virus transmission from their pets, most also reported increased caseloads, seeing newly adopted pets, and few discussions of surrender of pets for reasons related to the SARS-CoV-2 virus. CONCLUSIONS AND CLINICAL RELEVANCE: Findings indicated that caseloads increased and telehealth services expanded during the pandemic but that there was no evidence of differences in respondent-reported owner concern for SARS-CoV-2 virus transmission from cats versus dogs.

Alcohol and inflammatory responses: Highlights of the 2015 Alcohol and Immunology Research Interest Group (AIRIG) meeting.

On September 27, 2015 the 20th annual Alcohol and Immunology Research Interest Group (AIRIG) meeting was held as a satellite symposium at the annual meeting of the Society for Leukocyte Biology in Raleigh, NC. The 2015 meeting focused broadly on adverse effects of alcohol and alcohol-use disorders in multiple organ systems. Divided into two plenary sessions, AIRIG opened with the topic of pulmonary inflammation as a result of alcohol consumption, which was followed by alcohol's effect on multiple organs, including the brain and liver. With presentations showing the diverse range of underlying pathology and mechanisms associated with multiple organs as a result of alcohol consumption, AIRIG emphasized the importance of continued alcohol research, as its detrimental consequences are not limited to one or even two organs, but rather extend to the entire host as a whole.